A “pure” polymer is inherently a mixture of different molecules. These molecules have different molecular weights, and often, different configurations—depending upon the polymerisation conditions by which the polymer was formed from its monomer(s). As a result, the mode of polymerisation of the monomer determines the chemical structure and hence, all properties of the polymer. It is groundless and most often wrong to assume that all polymers from the one monomer are either the same or react in the same manner. In particular, acrolein (2-propene-1-al) has alternative reaction-sites and every “polyacrolein” is not the same.
The polymerisation of acrolein was first reported1 in 1843—providing a solid, insoluble in all common solvents, and of no significant use.
Much later in 1987, Melrose et al2 first described the manufacture, compositions and uses of a range of polymers of acrolein as anti-microbial agents; by demonstrating a structural analogy between the polymers and the chemical sterilant glutaraldehyde (pentane-1,5-dial), the carbonyls were assigned as the anti-microbial sites in the polymers. Since water is the growth-domain of nearly all micro-organisms, water-solubility or at least an ability to disperse is essential for anti-microbial activity against these micro-organisms; therefore, usually, the polymers also contained hydrophilic co-monomers, so as to make the polymers more water-soluble. But still, anti-microbial activity of the polymers remained low, due to their high content of co-monomer which only contributed hydrophilicity.
In an attempt to circumvent this limiting insolubility in water—subsequent references3-7 always requires firstly, the anionic homo-polymerisation of acrolein monomer only, to yield an insoluble polyacrolein. Therefore, this was followed by secondly, filtration of the resulting water-insoluble polymer—then thirdly, prolonged autoxidation of the polymer by heating in air or oxygen over several days, to yield the acrolein-polymer, poly (2-propenal, 2-propenoic acid) having a content of 0.1 to 5 moles of (hydrophilic) carboxyl/Kg of polymer, so as to achieve water-solubility, albeit only4 at pHs above 5.5. Fourthly, the auto-oxidised polymer may be treated with polyethylene glycol (PEG) over a range including both weakly basic then weakly acidic conditions, to yield an acrolein-polymer having increased hydrophilicity, and acetal groups derived from reaction with the polyethylene glycol. However, this sequential synthesis is substantially limited, in that its autoxidation-step is so protracted—and tenuous, due to the well-known propensity of acrolein-polymers to revert to insoluble gums during filtration, and especially upon heating—a property8 which had inhibited their use for over one hundred years. As a direct consequence of these disadvantages, this process can not be repeated, successfully, on a regular basis.
Within the gastro-intestinal tract of humans, the bacterium Helicobacter pylori10 may be harboured in tooth-plaque; also surrounded by protective natural polymers, it is found in the stomach of about 50% of persons world-wide. In humans, it is unequivocally associated with stomach and duodenal ulcers and cancer; noteworthy, the bacterium thrives within the acidic pHs of the stomach. Therapy for infected patients necessarily includes a regime of a range of different antibiotics—since it is increasingly being frustrated by strains of H. pylori which are resistant to known antibiotics. In animals, but with less certainty, other Helicobacter have also been associated with gastro-intestinal disease.
Always, soluble polymers of acrolein have shown an exceptionally wide range of anti-microbial activity—even against antibiotic-resistant germs—and this is explained by the polymers' content of carbonyl groups which react destructively and indiscriminately with ever-present proteins in the outer membranes of all micro-organisms. Particularly, Melrose et al7 have reported anti-microbial activity of the acrolein-polymer, poly (2-propenal, 2-propenoic acid) against H. pylori, in vitro at pH 4 or pH 7—but the polymer's water-solubility and anti-microbial activity is greatly reduced at the lower pHs associated with stomach-contents (that is, below pH 4).
Acrolein can be a source of extreme irritation to humans or animals3-7, 9. It is generally recognised that any molecule having molecular weight less than 800, reasonably freely passes through natural membranes (skin or intestines); thus, irritating acrolein-monomer, low molecular weight oligomers of acrolein or its acetals have the propensity to penetrate protective membranes in humans or animals and hence, enter the vascular system, causing irritation.
Specification WO 2005/044874 relates to a method for the manufacture of what are referred to as soluble, microbiologically active and stable acrolein polymers. Importantly, the polymer described is not derived directly from acrolein and is subject to the known problems associated with the initial filtration of a derived acrolein and is consequently limited by the formation of emulsions and gums. These issues have been highlighted4. The polymers produced by this method are not significantly anti-microbial and the minimum kill concentrations (MKC's) disclosed in the specification are known to involve a 24 hr exposure time. The method of manufacture described includes a number of limitation in addition to that noted immediately above. These include autoxidation/severe heating conditions at 65° C. and above (which are described as essential), derivation in acidic conditions, a requirement for subsequent treatment of the polymer with base to achieve stability, substantial degradation of the polymer as evidenced by the brown colour thereof, and the polymer derived in this manner is further poly-acetal and contains considerable carboxyl as is apparent from its dissolution in sodium carbonate solution (normally about pH 11) only giving a pH of 8 as the result of neutralisation of carboxyl.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.